Why Me? The Diabetes – Genes Autoimmunity and Prevention study may help find the answer.

 

 

A recent meeting heard from a young man who has lived with Type 1 diabetes for over 20 years recall that when diagnosed with diabetes, one of his frequent unanswered questions was, ‘Why me? Why not my other siblings or friends?’

Tim Tree explained how his desire to answer this question for himself, led him to a career in scientific research and to working on the Diabetes Genes, Autoimmunity and Prevention (D-GAP) study. Dr Tree described how working on this study has helped him, not to answer his question, but to understand how complex the question actually is. And he spoke passionately about how he believes the study is helping get closer to an answer. 

 

 

 

The D-GAP study, led by Professor Mark Peakman is looking to uncover the connections between genes, the body's immune response and Type 1 diabetes. Specifically, they are trying to establish if some of the genes linked to Type 1 diabetes directly affect our ‘immune phenotype’ – the characteristics of our bodies’ immune systems. By confirming this link, the causative immune phenotypes in Type 1 diabetes would be identified. In turn these could become the targets for drug development, or specific blood markers for measuring success in clinical trials testing new methods for treating or even preventing Type 1 diabetes.

 

Each cell in your body contains chromosomes. Chromosomes are made up of a catalogue of genes – sections of DNA that act as a ’recipe books’ with instructions for how to make all of machinery a cell needs to fulfil it’s role in the body. The particular selection of gene recipes we inherit from our parents determines our biological make up. For example, there are six genes which contribute to determining your eye colour and different ‘flavours’ or natural variations in these genes influence whether you have blue eyes or brown eyes. In the D-GAP study, researchers are examining how different flavours of genes associated with type 1 diabetes can make you more or less susceptible to developing Type 1 diabetes. 

The D-GAP team are asking the brothers and sisters of young people with Type 1 diabetes, diagnosed before the age of 16 to take part in the study. These brothers and sisters share much of the same genetic ‘recipe book’ as the young person with Type 1 diabetes. It’s therefore likely that some of the siblings, although they do not have diabetes, will have the genes which could predispose them to the condition. 

The study also needs young people aged five to 35 years old who have been diagnosed with Type 1 diabetes within the last three months. This will allow the team to look at what happens to the immune system in the early stages of the condition. 

People who volunteer to take part in the study are asked to provide an initial saliva sample, from which DNA can be isolated to allow scientist to study their genetic make up. Roughly one out of every five people who volunteer to take part.

 

Immunity is how our bodies learn to protect us from harmful attack – for examplefrom parasites or viruses. Our bodies develop immuntiy both passively (passed on from mother) or actively (through exposure or inoculation). Autoimmunity is where the body mistakenly identifies part of itself as being harmful, leading to the body to launch an immune attack against its own tissues. In Type 1 diabetes, that autoimmune reaction is directed at the insulin producing beta cells of the pancreas. 

T cells are a group of white blood cells that play a central role in immunity. Through receptor molecules on their surfaces, T cells directly attack cells and particles that they identify as ‘foreign’ or harmful. To do this, they bind to the ‘foreign’ particle and trigger a reaction to destroy them and remove them from the body. There are many millions of T cells in our bodies, with a huge variety of receptors. This enables our bodies to repond quickly and efficiently to virtually any foreign body. 

There are two very important types of T cells that have a key role in type 1 diabetes. Autoreactive T cells are cells that recognise and attack the beta cells in the pancreas. Regulatory T cells exist to control this over zealous response.  The D-GAP study is attempting to track down and study the autoreactive T cells that attack the beta cells, by measuring the levels of these ‘bad’ T cells in both people without diabetes, and in people who have just been diagnosed with the condition. 

The researchers expect to find few autoreactive T cells in people without diabetes and lots in people newly diagnosed. They also hope to show that measuring levels of regulatory T cells could be used to predict age of onset in people at risk of developing type 1 diabetes. The researchers predict that lower levels of regulatory cells will indicate a younger age of onset of type 1 diabetes. If this work is successful, the research team hope to identify treatments that could redress the balance between regulatory T cells and autoreactive T cells – encouraging more regulatory cells and reducing numbers of autoreactive T cells. 

 

Your genetic make up is a blueprint for the development of all the cells in your body. In some people, this blueprint contains different ‘flavours’ of particular genes that can increase their likelihood of developing Type 1 diabetes. Some of these natural variations cause the immune system to produce too many autoreactive T cells that react to the insulin producing beta cells for the regulatory T cells to be able to control. 

The D-GAP researchers are attempting to identify these variations by comparing DNA samples from those with and without Type 1 diabetes. In addition, they are measuring the levels of regulatory and autoreactive T cells in people newly diagnosed to provide evidence that the level of imbalance between these cell types determines the age of onset of Type 1 diabetes.

At present people in Ireland cannot take part in the study, but the Diabetes Ireland Research Alliance is working with the research team to see if it is possible to recruit participants in Ireland.

The D-GAP study is currently only examining the genetic aspect of developing Type 1 diabetes and therefore is examining only one part of the puzzle about  what triggers the development of Type 1 diabetes. While we know that genetic predisposition is a vital part of this equation, we also know that something else, a so-called ‘environmental factor’, is also necessary. Even though much other research around the world is focusing on finding out what this factor might be, scientists have as yet been unable to identify it – which probably means there is a complex combination of factors at play. 

 

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